Central nervous system macrophages in progressive multiple sclerosis: relationship to neurodegeneration and therapeutics

Journal of Neuroinflammation

Cole Libner¹  Emily Kamma²  Huah Shin Ng³  Jason R. Plemel⁴  Wendy Lasisi⁵ 

[1] Department of Health Sciences and the Office of the Saskatchewan Multiple Sclerosis Clinical Research Chair, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada;Division of Neurology and the Djavad Mowafaghian Centre for Brain Health, Department of Medicine, University of British Columbia, Vancouver, BC, Canada;Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada;Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada;Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada;University of Alberta, 5-64 Heritage Medical Research Centre, T6G2S2, Edmonton, AB, Canada;Recovery and Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland, Saint John’s, NL, Canada;

关键词: Macrophages;    Microglia;    Multiple sclerosis;    Neurodegeneration;    Primary progressive;    Secondary progressive;    Therapeutics;   

DOI  :  10.1186/s12974-022-02408-y

来源: Springer

【 摘 要 】

There are over 15 disease-modifying drugs that have been approved over the last 20 years for the treatment of relapsing–remitting multiple sclerosis (MS), but there are limited treatment options available for progressive MS. The development of new drugs for the treatment of progressive MS remains challenging as the pathophysiology of progressive MS is poorly understood.The progressive phase of MS is dominated by neurodegeneration and a heightened innate immune response with trapped immune cells behind a closed blood–brain barrier in the central nervous system. Here we review microglia and border-associated macrophages, which include perivascular, meningeal, and choroid plexus macrophages, during the progressive phase of MS. These cells are vital and are largely the basis to define lesion types in MS. We will review the evidence that reactive microglia and macrophages upregulate pro-inflammatory genes and downregulate homeostatic genes, that may promote neurodegeneration in progressive MS. We will also review the factors that regulate microglia and macrophage function during progressive MS, as well as potential toxic functions of these cells. Disease-modifying drugs that solely target microglia and macrophage in progressive MS are lacking. The recent treatment successes for progressive MS include include B-cell depletion therapies and sphingosine-1-phosphate receptor modulators. We will describe several therapies being evaluated as a potential treatment option for progressive MS, such as immunomodulatory therapies that can target myeloid cells or as a potential neuroprotective agent.

【 授权许可】

CC BY